Chronic kidney disease (CKD) has emerged as a serious complication of lung transplantation. Not only is it a common occurrence but is one that is associated with significant morbidity and even mortality. There have been no prospective studies that addressed this problem. Therefore, we propose a concerted effort to more accurately define pretransplant kidney function and structure in candidates for lung transplants and to further characterize the evolution of kidney structure and function in the fist 4 years after transplantation. More specifically, we will determine the prevalence of CKD as assessed by measured GFR, urinary albumin excretion and careful histological evaluation of renal tissue obtained around the time of the lung transplantation. The longitudinal studies proposed will define the impact of lung transplantation on renal structure and function. Subjects who underwent a kidney biopsy at the time of transplantation will undergo a repeat kidney biopsy at 1 and 4 years. These studies will address whether current utilization of serum creatinine-based formulas and 24-hour creatinine clearance underestimate the prevalence of chronic kidney disease in candidates for lung transplantation and detailed renal histological examinationwill reveal progressive arteriolar hyalinosis, worsening glomerulosclerosis, and expansion of the cortical interstitial: all major contributors to renal fibrosis and renal death. In addition to our correlational studies of structure and function, we will assemble a repository of serial urinary samples that will be subjected to proteomic analysis in an attempt to detect potential biomarkers that may precede the functional and structural renal deterioration. The unprecedented planned detailed studies of kidney structure in lung transplant recipients and our ability to recruit and retain subjects in long-term studies of kidney structure will translate into a body of knowledge that will ultimately aid in designing interventional trials for a condition that lacks major therapeutic options.

Public Health Relevance

The proposed detailed studies of renal function and structure will carefully profile the evolution of renal deterioration after lung transplantation which will not only address a common problem but has a potential of aiding our understanding of chronic kidney disease,in the setting of other solid organ transplants.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Special Emphasis Panel (ZDK1-GRB-R)
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University of Minnesota Twin Cities
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